Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol SESN2 contributors: mct - updated : 06-01-2016
HGNC name sestrin 2
HGNC id 20746
Location 1p35.3      Physical location : 28.586.005 - 28.609.001
Synonym name hypoxia induced gene 95
Synonym symbol(s) HI95, SES2, DKFZp761M02121, SEST2, DKFZp761M0212
DNA
TYPE functioning gene
STRUCTURE 23.00 kb     10 Exon(s)
Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
10 - 3503 - 480 - 2002 12203114
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveliver    
Endocrinepancreas    
Nervousbrain    
Respiratorylung    
Urinarykidney    
cells
SystemCellPubmedSpeciesStageRna symbol
Endocrineislet cell (alpha,beta...)
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
HOMOLOGY
interspecies homolog to murine Sesn2 (91.5pc)
Homologene
FAMILY
  • sestrin family of PA26-related proteins
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    basic FUNCTION
  • may be involved in cellular response to different stress conditions (Budanov 2002)
  • may function in the regulation of cell growth and survival
  • involved in the induction of autophagy in TP53-proficient cells (Maiuri 2009)
  • exhibit oxidoreductase activity and may function as antioxidants (Lee 2010)
  • important negative feedback regulator of MTOR whose loss results in various MTOR-dependent, age-related pathologie (Lee 2010)
  • important homeostatic function for the stress-inducible Sestrin protein family SESN2 and SESN3 in the control of mammalian lipid and glucose metabolism
  • is a new energetic stress sensor, which appears to be protective against energetic stress-induced apoptosis that integrates the pro-survival function of AKT1 and the negative regulation of MTOR
  • antioxidant function of SESN2 limits neuropathic pain processing
  • SESN2 and AMP-activated protein kinase (AMPK), important for the maintenance of metabolic homeostasis, are also stress-inducible proteins that are critical for the suppression of ROS production and protection from oxidative stress
  • SESN2 and antioxidants inhibit UCP1 expression through suppressing ROS-mediated MAPK14 activation, implying a critical role of ROS in proper BAT metabolism
  • autophagy-controlling function of SESN2 may be important for its other physiological functions
  • is a promoter of ULK1-mediated SQSTM1 phosphorylation
  • conserved antioxidant protein that accumulate in cells in response to various stresses
  • inhibits TLR-induced proinflammatory signaling and protects cells by inhibiting JNK- or MAPK14-mediated JUN phosphorylation
  • is likely a crucial modulator for the production of reactive oxygen species (ROS)
  • transient global ischemia (TGI)-induced SESN2 expression contributed to RPS6 phosphorylation and neuroprotection against ischemic injury in the hippocampal CA1 subfield
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • stress-inducible protein known to activate AMPK
  • NFE2L2-ARE pathway is critical for SESN2 gene expression and might protect against oxidative stress
  • SESN1 and SESN2 interact with the NFE2L2 suppressor KEAP1, the autophagy substrate SQSTM1, and the ubiquitin ligase RBX1 and the antioxidant function of SESNs is mediated through activation of NFE2L2 in a manner reliant on SQSTM1-dependent autophagic degradation of KEAP1
  • induction of SESN2 acts as a compensatory response to AGT for survival, and protects against endothelial toxicity of AGT
  • DRD2, via paraoxonase 2 and SESN2, keeps normal renal redox balance, which contributes to the maintenance of normal blood pressure
  • stress-inducible protein, recently been shown to bind to SQSTM1 and promoting autophagic degradation of such SQSTM1 targets
  • physically associates with Unc-51-like protein kinase 1 (ULK1) and SQSTM1 to form a complex in which both SESN2 and SQSTM1 become phosphorylated by ULK1 at multiple sites
  • SESN2 may also regulate RPS6, a molecule important for protein synthesis, through the effect of MTOR complex that is pivotal for longevity
  • role of ATF4 in the SESN2 gene upregulation induced by mitochondrial dysfunction
  • cell & other
    REGULATION
    induced by hypoxia
    Other up-regulated expression following DNA damage or oxidative stress
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cardiovascularaquired 
    stimulating expression of SESN2 might be an effective pharmacological target for the treatment of AGT-associated cardiovascular diseases
    miscelleaneouspain 
    potential new target for the clinical management of chronic neuropathic pain conditions
    ANIMAL & CELL MODELS
  • Sesn2 knockout (Sesn2(-/-)) mice exhibited considerably increased late-phase neuropathic pain behavior, while their behavior in acute nociceptive and in inflammatory pain models remained unaffected